肝星状细胞激活与增殖相关信号转导通路在肝纤维化中的作用及机制

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (4): 455-459.

肝星状细胞激活与增殖相关信号转导通路在肝纤维化中的作用及机制

鲍佳春¹, 袁凤来¹, 陆伟国¹, 李霞^1,2, 吴繁荣², 陈飞虎²

¹无锡市第三人民医院, 无锡214041, 江苏;
²安徽医科大学药学院, 安徽230031, 合肥

收稿日期:2009-03-30 修回日期:2009-04-23 发布日期:2020-10-29
作者简介:鲍佳春,女,药师,研究方向:分子药理学。Tel:0510-82607391 E-mail:yinminyue@126.com。陈飞虎,男,博士,教授,博士生导师,研究方向:分子药理学。Tel:0551-25161115 E-mail:cfhchina@sohu.com
基金资助:
安徽省自然科学资金(090413139);安徽省科技攻关重点资助项目(07010302178)

Effects and mechanisms of hepatic stellate cells (HSC)activation and proliferation-related signal transduction pathway in liver fibrosis

BAO Jia-chun¹, YUAN Feng-lai¹, LU Wei-guo¹, LI Xia^1,2, WU Fan-rong², CHEN Fei-hu²

¹Wuxi Third People's Hospital, Wuxi 214041, Jiangsu, China;
²College of Pharmacy, Anhui Medical University,Hefei 230032, Anhui, China

Received:2009-03-30 Revised:2009-04-23 Published:2020-10-29

摘要/Abstract

摘要： 肝星状细胞激活和增殖在肝纤维化的发生过程中占有重要的地位。控制肝星状细胞的激活和增殖并逆肝纤维化的进程是抗肝纤维化研究的重点之一。本综述以肝星状细胞激活与增殖相关信号转导通路为中心,探讨其在肝纤维化发病作用方面的作用机制。通过干预细胞外信号传导通路,为研究肝纤维化的发病机制和药物治疗提供新的途径。

关键词: 星状细胞, 肝纤维化, 信号转导通路

Abstract: The activation and proliferation of hepatic stellate cell(HSC)have been considered to play an important role in hepatic fibrosis.The manipulation of the activation and proliferation of hepatic stellate cells and the process of liver fibrosis inversion are the key in anti-liver-fibrosis researches.This paper briefly reviews the hepatic stellate cells (HSC)activation and proliferation-related signal transduction pathway and explores the role in the pathogenesis of liver fibrosis.It is a new way to study the pathogenesis and therapy of liver fibrosis through intervention of HSC activation and proliferation-related signal transduction pathway.

Key words: hepatic stellate cell, liver fibrosis, signal pathways

中图分类号:

R575.5

鲍佳春, 袁凤来, 陆伟国, 李霞, 吴繁荣, 陈飞虎. 肝星状细胞激活与增殖相关信号转导通路在肝纤维化中的作用及机制[J]. 中国临床药理学与治疗学, 2009, 14(4): 455-459.

BAO Jia-chun, YUAN Feng-lai, LU Wei-guo, LI Xia, WU Fan-rong, CHEN Fei-hu. Effects and mechanisms of hepatic stellate cells (HSC)activation and proliferation-related signal transduction pathway in liver fibrosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(4): 455-459.

参考文献

[1] Friedman SL.The cellular basis of hepatic fibrosis[J].N Engl JMed, 1993, 328(25):1828-1835.
[2] Minicis SD, Candelaresi C, Marzioni M, et al.Role of endogenous opioids in modulating HSC activity in vitro and liver fibrosis in vivo[J].Gut, 2008, 57(3):352-364.
[3] Yuan LP, Chen FH, Ling L, et al.Protective effects of total flavonoids of Bidens bipinnata L.against carbon tetrachloride-induced liver fibrosis in rats[J].J Pharm Pharmacol, 2008, 60(10):1393-1402.
[4] Friedman SL.Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury [J].J Biol Chem, 2000, 275(4):2247-2250.
[5] Su GL.Lipopolysaccharides in liver injury:molecular mechanisms of Kupffer cell activation[J].Am J Physiol Gastrointest Liver Physiol, 2002, 283(2):256-265.
[6] Lewindon PJ, Pereira TN, Hoskina AC, et al.Role of hepatic stellate cells and transforming growth factor-β in cystic fibrosis liver disease[J].Am J Pathol, 2002, 160(5): 1705-1715.
[7] Elsharkawy AM, Oakley F, Mann DA.The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis[J].Apoptosis, 2005, 10(5):927-939.
[8] 吴繁荣, 陈飞虎, 胡伟, 等.鬼针草总黄酮抗大鼠免疫性肝纤维化作用及部分机制研究[J].中国药理学通报, 2008, 24(6):753-756.
[9] 蒋明德.肝纤维化发生中的MAPK 信号传导通路[J].第四军医大学学报, 2005, 26(8):766-767.
[10] Kim WH, Matsumoto K, Bessho K, et al.Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis [J].Am J Pathol, 2005, 166(4):1017-1028.
[11] Tsukada S, Parsons CJ, Rippe RA.Mechanisms of liver fibrosis[J].Clin Chim Acta, 2006, 364 (1 2):33-60.
[12] Jung JO, Gwak GY, Lim YS, et al.Role of hepatic stellate cells in the angiogenesis of hepatoma[J].Korean J Gastroenterol, 2003, 42(2):142-148.
[13] Dent P, Yacoub A, Fisher PB, et al.MAPK pathways in radiation responses[J].Oncogene, 2003, 22(37):5885-5896.
[14] Sohn JH, Han KL, Kim JH, et al.Protective Effects of macelignan on cisplatin induced hepatotoxicity is associated with JNK activation[J].Biol Pharm Bull, 2008, 31(2):273-277.
[15] Furukawa F, Matsuzaki K ,Mori S, et al.p38 MAPK mediates fibrogenic signal through Smad3 phosphorylation in rat myofibroblasts[J].Hepatology, 2003, 38(4):879-889.
[16] Reif S, LangA, Lindquist JN, et al.The role of focal adhesion kinase phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type Ⅰ collagen expression[J].J Biol Chem, 2003, 278(10):8083-8090.
[17] Gabele E, Reif S, Tsukada S, et al.The role of p7056K in hepatic stellate cell collagen gene expression and cell proliferation[J].J Biol Chem, 2005, 280(14):13374-13382.
[18] Saxena NK, Ikeda K, Rockey DC, et al.Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob ob mice[J].Hepatology, 2002, 35(4):762-771.
[19] Hegyi K, Fulop K, Kovacs K, et al.Leptin-induced signal transduction pathway s[J].Cell Biol Int, 2004, 28(3):159-161.
[20] Novitskiy G, Ravi R, Potter JJ, et al.Effects of acetaldehyde and TNF alpha on the inhibitory kappa B-alpha protein and nuclear factor kappa B activation in hepatic stellate cells[J].Alcohol, 2005, 40(2):96-101.
[21] Lang A, Schoonhoven R, Tuvia S, et al.Nuclear factor kappa B inproliferation, activation, and apoptosis in rat hepatic stellate cells[J].J Hepatol, 2000, 33(1):49-58.
[22] Gao R, Brigstock DR.Activation of nuclear factor kappa B(NF-kappa B)by connective tissue growth factor (CCN2)is involved in sustaining the survival of primary rat hepatic stellate cells[J].Cell Commun Signal, 2005, 22(3):14.
[23] Sun K,Wang Q, Huang XH.PPAR gamma inhibits growth of rat hepatic stellate cells and TGF beta-induced connective tissue growth factor expression[J].Acta Pharmacol Sin, 2006, 27(6):715-723.